Correlation between human epidermal growth factor receptor 2 oncoprotein expression and some prognostic factors in papillary thyroid carcinoma

Rabiee, Shervin; Nadoushan, Mohammadreza Jalali; Rayeni, Neda Mehdizade; Ansari, Iman

doi:10.4103/ijpm.ijpm_332_15

Cited by 4 publications

(8 citation statements)

References 1 publication

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“…One unique mechanism by which thyroid cancer drives RAI resistance may be via upregulation of the human epidermal receptor (HER) family of receptor tyrosine kinases, which is present in more than one-third of thyroid cancers and is positively correlated with local tumor invasiveness [52]. HER2 and HER3 are key players upstream of extracellular signal-regulated kinase (ERK) and AKT, and HER2 and HER3 activate these signaling pathways.…”

Section: Management Of Rai-r Thyroid Cancersmentioning

confidence: 99%

Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies

Aashiq

Silverman

Na’ara

et al. 2019

Cancers

107

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Recurrent, metastatic disease represents the most frequent cause of death for patients with thyroid cancer, and radioactive iodine (RAI) remains a mainstay of therapy for these patients. Unfortunately, many thyroid cancer patients have tumors that no longer trap iodine, and hence are refractory to RAI, heralding a poor prognosis. RAI-refractory (RAI-R) cancer cells result from the loss of thyroid differentiation features, such as iodide uptake and organification. This loss of differentiation features correlates with the degree of mitogen-activated protein kinase (MAPK) activation, which is higher in tumors with BRAF (B-Raf proto-oncogene) mutations than in those with RTK (receptor tyrosine kinase) or RAS (rat sarcoma) mutations. Hence, inhibition of the mitogen-activated protein kinase kinase-1 and -2 (MEK-1 and -2) downstream of RAF (rapidly accelerated fibrosarcoma) could sensitize RAI refractivity in thyroid cancer. However, a significant hurdle is the development of secondary tumor resistance (escape mechanisms) to these drugs through upregulation of tyrosine kinase receptors or another alternative signaling pathway. The sodium iodide symporter (NIS) is a plasma membrane glycoprotein, a member of solute carrier family 5A (SLC5A5), located on the basolateral surfaces of the thyroid follicular epithelial cells, which mediates active iodide transport into thyroid follicular cells. The mechanisms responsible for NIS loss of function in RAI-R thyroid cancer remains unclear. In a study of patients with recurrent thyroid cancer, expression levels of specific ribosomal machinery—namely PIGU (phosphatidylinositol glycan anchor biosynthesis class U), a subunit of the GPI (glycosylphosphatidylinositol transamidase complex—correlated with RAI avidity in radioiodine scanning, NIS levels, and biochemical response to RAI treatment. Here, we review the proposed mechanisms for RAI refractivity and the management of RAI-refractive metastatic, recurrent thyroid cancer. We also describe novel targeted systemic agents that are in use or under investigation for RAI-refractory disease, their mechanisms of action, and their adverse events.

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Section: Management Of Rai-r Thyroid Cancersmentioning

confidence: 99%

Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies

Aashiq

Silverman

Na’ara

et al. 2019

Cancers

107

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“…Jumlah sampel penelitian Mohapatra pada tahun 2019 adalah 25 sampel dengan 20 sampel tanpa invasi kapsular. 8,9 Delia pada tahun 2017 menemukan bahwa HER2 menunjukkan ekspresi yang berbeda pada variasi subtipe histologi PTC. 10 Penelitianpenelitian yang telah dilakukan tersebut masih terdapat kontradiksi, sehingga masih diperlukan penelitian lebih lanjut mengenai hubungan HER2 terhadap ukuran tumor dan invasi kapsular sebagai faktor prognosa PTC.…”

Section: Pendahuluanunclassified

“…Serta didapatkan rerata nilai skor HER2 yang lebih tinggi pada kelompok dengan invasi kapsular dan tidak. [8][9][10][11] Namun, penelitian lebih lanjut dibutuhkan karena besarnya HER2 yang bernilai equivocal perlu dikorelasikan dan dilanjutkan dengan pemeriksaan FISH.…”

Section: Pembahasanunclassified

“…Selain itu, pada data Mohapatra dan Rabiee sampel lebih banyak pada usia <45 tahun, berbeda dengan sampel penelitian ini yang lebih banyak pada usia >45 tahun. 8,9 Beberapa penelitian telah dilakukan untuk mengkaji apakah ekspresi HER2 berhubungan dengan faktor prognosis PTC. Namun, masih terdapat kontroversi apakah HER2 memiliki peranan dalam menentukan faktor prognostik.…”

Section: Pembahasanunclassified

“…Pada penelitian Cau, Rabie, Caria, Delia dan Mohapatra menyebutkan bahwa terdapat hubungan antara ekspresi HER2 dengan faktor prognostik. [8][9][10]18,22 Sementara pada penelitian Balta dan Kim menyatakan tidak ada hubungan antara ekspresi HER2 dengan faktor prognostik. 6,7 Perbedaan ekspresi HER2 dipengaruhi oleh kualitas preanalitik sampel, reagen, profil sampel dan profil molekuler yang dimiliki tumor tersebut.…”

Section: Pembahasanunclassified

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Hubungan Ekspresi Her2 Dengan Ukuran Tumor Dan Invasi Kapsular Papillary Thyroid Carcinoma (Ptc)

Pinahayu

Retnani

Anita

et al. 2021

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Papillary thyroid carcinoma (PTC) merupakan karsinoma tersering pada tiroid yang secara klinis dapat menyerupai lesi jinak. PTC subtipe ocult tidak jarang ditemukan bermetastase pada kelenjar getah bening (KGB) atau organ lain. Faktor prognosis pada pasien PTC ditentukan oleh subtipe histologi, ukuran tumor, usia, jenis kelamin, metastase dan invasi kapsular, dengan angka kekambuhan cukup tinggi, yaitu 20%. Human Epidermal Growth Factor Receptor 2 (HER2) adalah anggota Epithelial Growth Factor Receptor (EGFR), yang menunjukkan ekspresi kuat pada keganasan sel epitel manusia. Penelitian ini bertujuan untuk melihat hubungan ekspresi HER2 dengan ukuran tumor dan invasi kapsular PTC. Pemeriksaan histopatologi dan imunohistokimia HER2 dilakukan pada 54 sampel, 27 dengan invasi kapsular dan 27 tanpa invasi kapsular, kemudian diukur besar tumor, interpretasi ekspresi HER2, lalu ditabulasi dan dianalisis hubungan ekspresi HER2 dengan ukuran tumor dan invasi kapsular PTC. Ekspresi HER2 pada penelitian ini didapatkan pada 10 sampel HER2 skor 3+, 22 sampel skor 2+, 14 sampel skor 1+, dan 8 sampel skor 0. Hubungan antara ekspresi HER2 dengan invasi kapsular PTC, dianalisis dengan Mann Whitney test, didapatkan hasil bermakna (p = 0,002). Dengan uji korelasi Spearman, didapatkan korelasi lemah terbalik (koefisien korelasi -.299) tapi bermakna (p = 0,028) antara ekspresi HER2 dengan ukuran tumor PTC. Terdapat hubungan ekspresi HER2 dengan invasi kapsular, dan hubungan lemah berbanding terbalik antara ekspresi HER2 dengan ukuran tumor yaitu semakin besar ukuran tumor semakin rendah skor HER2 dan sebaliknya. Kata Kunci: HER2, invasi kapsular PTC, ukuran tumor PTC.

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Molecular basis and targeted therapies for radioiodine refractory thyroid cancer

Zhang

et al. 2022

Asia-Pac J Clncl Oncology

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Patients diagnosed with radioiodine refractory thyroid cancer (RAIR-TC) are not amenable to novel 131 I therapy due to the reduced expression of sodium iodide symporter (Na+/I-symporter, NIS) and/or the impairment of NIS trafficking to the plasma membrane. RAIR-TC patients have a relatively poor prognosis with a mean life expectancy of 3-5 years, contributing to the majority of TC-associated mortality. Identifying RAIR-TC patients and selecting proper treatment strategies remain challenging for clinicians. In this review, we demonstrate the updated clinical scenarios or the socalled "definitions" of RAIR-TC suggested by several associations based on 131 I uptake ability and tumor response post-131 I therapy. We also discuss current knowledge of the molecular alterations involved in membrane-localized NIS loss, which provides a preclinical basis for the development of targeted therapies, in particular, tyrosine kinase inhibitors (TKIs), redifferentiation approaches, and immune checkpoint inhibitors.

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Correlation between human epidermal growth factor receptor 2 oncoprotein expression and some prognostic factors in papillary thyroid carcinoma

Abstract: HER2 oncoprotein expression is correlated with increased tumor size and capsular invasion. Hence, HER2 can be used to assess PTC prognosis.

Cited by 4 publications

References 1 publication

Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies

Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies

Hubungan Ekspresi Her2 Dengan Ukuran Tumor Dan Invasi Kapsular Papillary Thyroid Carcinoma (Ptc)

Molecular basis and targeted therapies for radioiodine refractory thyroid cancer

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